본문 바로가기
KERD
논문KCI 등재

Anticancer Effects of Typhae Pollen on HepG2 Human Hepatocellular Carcinoma

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류한의학

초록

The aim of this study was to evaluate the antitumor activities of Typhae pollen (TP) by confirming in vitro cytotoxicity and in vivo anti-tumor and immune-modulatory effect with anti-cachexia effect. The MTT assay is used in HepG2 cell to detect potential cytotoxic activities of aqueous extract of Typhae pollen (TPe). After HepG2 tumor cell implantation, eight mice per groups were assigned to six groups. Three different dosages of TPe (500, 250 and 125 ㎎/㎏) were orally administered in the amount of 10 ㎖/㎏ and sorafenib also administered 20㎎/㎏, every day for 35 days from 28 days after the tumor cell implantation. We observed the changes on body weights, tumor volume and weights, lymphatic organ, serum interferon (IFN)-γ levels, splenocytes and peritoneal NK cell activity, splenic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10 contents. Periovarian fat weights, serum IL-6 levels, thicknesses of deposited periovarian adipose tissue and mean diameters were also detected to monitor the tumor-related anticachexic effects. In tumor masses, the immunoreactivities of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (cleaved PARP) - apoptotic marks, cyclooxygenase-2 (COX-2), inducible nitric oxide synthases (iNOS) and tumor necrosis factor (TNF)-α were additionally observed by immunohistochemistry. The results were compared with sorafenib. Decreases of COX-2 were demonstrated in sorafenib and TPe treated mice and also increases of iNOS in tumor masses were observed in TPe, not in sorafenib. TPe increased periovarian fat pad weights compared with tumor-bearing controls and sorafenib treated mice. TPe showed increases of splenic TNF-α, IL-10 and IL-1β, serum IFN-γ and NK cell activities corresponding to increases of spleen weights, lymph node weights and non-atrophic changes of lymph nodes. Our results show oral treatment of TPe 500, 250 and 125 ㎎/㎏ has potent in vitro and in vivo antitumor activities through modest cytotoxic effects, immunomodulatory effects and apoptotic activities in HepG2 tumor cells. In addition, TPe can prevent cancer related cachexia.

Abstract

The aim of this study was to evaluate the antitumor activities of Typhae pollen (TP) by confirming in vitro cytotoxicity and in vivo anti-tumor and immune-modulatory effect with anti-cachexia effect. The MTT assay is used in HepG2 cell to detect potential cytotoxic activities of aqueous extract of Typhae pollen (TPe). After HepG2 tumor cell implantation, eight mice per groups were assigned to six groups. Three different dosages of TPe (500, 250 and 125 ㎎/㎏) were orally administered in the amount of 10 ㎖/㎏ and sorafenib also administered 20㎎/㎏, every day for 35 days from 28 days after the tumor cell implantation. We observed the changes on body weights, tumor volume and weights, lymphatic organ, serum interferon (IFN)-γ levels, splenocytes and peritoneal NK cell activity, splenic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10 contents. Periovarian fat weights, serum IL-6 levels, thicknesses of deposited periovarian adipose tissue and mean diameters were also detected to monitor the tumor-related anticachexic effects. In tumor masses, the immunoreactivities of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (cleaved PARP) - apoptotic marks, cyclooxygenase-2 (COX-2), inducible nitric oxide synthases (iNOS) and tumor necrosis factor (TNF)-α were additionally observed by immunohistochemistry. The results were compared with sorafenib. Decreases of COX-2 were demonstrated in sorafenib and TPe treated mice and also increases of iNOS in tumor masses were observed in TPe, not in sorafenib. TPe increased periovarian fat pad weights compared with tumor-bearing controls and sorafenib treated mice. TPe showed increases of splenic TNF-α, IL-10 and IL-1β, serum IFN-γ and NK cell activities corresponding to increases of spleen weights, lymph node weights and non-atrophic changes of lymph nodes. Our results show oral treatment of TPe 500, 250 and 125 ㎎/㎏ has potent in vitro and in vivo antitumor activities through modest cytotoxic effects, immunomodulatory effects and apoptotic activities in HepG2 tumor cells. In addition, TPe can prevent cancer related cachexia.

참고문헌 (41)

  1. Llovet JM, "Sorafenib in advanced hepatocellular carcinoma", N Engl J Med, 359, pp.378~390 (2008)[DOI]
  2. Colagrande S, "Challenges of advanced hepatocelluar carcinoma", World J Gastroenterol, 22(34), pp.7645~7659 (2016)[DOI]
  3. Mazzanti R, "Hepatocellular carcinoma : where are we?", World J exp Med, 6(1), pp.21~36 (2016)[DOI]
  4. Xin-Lei Gong, "Progress in systemic therapy of advanced hepatocellular carcinoma", World J Gastroenterol, 22(29), pp.6582~6594 (2016)[DOI]
  5. Tang, Z.Y., "Combination of traditional Chinese medicine and western medicine in the treatment of liver cancer", J. Clin. Hepatol., 27, pp.44950~ (2011)
  6. Wu, M.C., "Traditional Chinese medicine in prevention and treatment of liver cancer: Function, status and existed problems", J. Chin. Integr. Med., 1, pp.163164~ (2003)
  7. 이병찬, "포황(蒲黃)의 성분분석과 생리활성", Korean Journal of Agricultural Science, 36(2), pp.185~197 (2009), 농업과학연구소
  8. In-Young Choi, "Typha orientalis inhibits inflammatory cytokine expression through suppression of ERK phosphorylation in HMC-1 cells", Oriental Pharmacy and Experimental Medicine, 10(1), pp.7~12 (2010), 융합한의과학연구소
  9. 진경숙, "통초, 필발을 포함한 7종 한약재 추출물의 항산화 및 항염증 활성", 한국미생물·생명공학회지, 41(2), pp.253~262 (2013), 한국미생물·생명공학회[DOI]
  10. Lee H, "SH21B, an anti-obesity herbal composition, inhibits fat accumulation in 3T3-L1 adipocytes and high fat diet-induced obese mice through the modulation of the adipogenesis pathway", J Ethnopharmacol, 127, pp.709~717 (2010)[DOI]
  11. Jeon S, "A modified formulation of Chinese traditional medicine improves memory impairment and reduces <TEX>$A{\beta}$<", TEX> level in the Tg-APPswe, J Ethnopharmacol, pp.2011, 137[DOI]
  12. Ohkura N, "Experimental study on the hemostatc activity of Pollen Typhae: a traditional folk medicine used by external and oral application", Blood Coagul Fibrinolysis, 22(8), pp.631~636 (2011)[DOI]
  13. 진수정, "포황 메탄올 추출물에 의한 인체 대장암 세포주 HT29의 G2", M Arrest 및 Apoptosis 유발, 2013, pp.41(4), 425~432[DOI]
  14. Flecknell P, "Laboratory Animal Anesthesia", pp.269~ (1996), Harcourt Brace & Company
  15. Tai WT, "Mcl-1-dependent activation of Beclin 1 mediates autophagic cell death induced by sorafenib and SC-59 in hepatocellular carcinoma cells", Cell Death Dis, 4, pp.e485~ (2013)[DOI]
  16. Wang L, "A novel monoclonal antibody to fibroblast growth factor 2 effectively inhibits growth of hepatocellular carcinoma xenografts", Mol Cancer Ther, 11, pp.864~872 (2012)[DOI]
  17. Nishimura G, "An antioxidant, probucol, induces anti-angiogenesis and apoptosis in athymic nude mouse xenografted human head and neck squamous carcinoma cells", Jpn J Cancer Res, 90, pp.1224~1230 (1999)[DOI]
  18. Iizuka N, "Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6", Cancer Lett, 158, pp.35~41 (2000)[DOI]
  19. Hubbell HR, "Antiproliferative and immunomodulatory actions of beta-interferon and double-stranded RNA, individually and in combination, on human bladder tumor xenografts in nude mice", Cancer Res, 45, pp.2481~2486 (1985)
  20. Strayer DR, "Low natural killer cytotoxicity of peripheral blood mononudear cells in individ uals with high familial incidences of cancer", Cancer Res, 44, pp.370~374 (1984)
  21. Hotchkiss RS, "Calcium antagonists decrease plasma and tissue concentrations of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-1 alpha in a mouse model of endotoxin", Shock, 3, pp.337~342 (1995)
  22. 윤현수, "Immunomodulatory Effects of Aureobasidium pullulans SM-2001 Exopolymers on Cyclophosphamide-Treated Mice", Journal of Microbiology and Biotechnology, 20(2), pp.438~445 (2010), 한국미생물·생명공학회
  23. Park JC, "In vivo and In vitro antitumor effects of Platycodin D, a saponin purified from Platycodi Radix on the H520 lung cancer cell", Evid Based Complement Alternat Med, 2014, pp.478653~ (2014)
  24. Jung YM, "Fermented garlic protects diabetic, obese mice when fed a high-fat diet by antioxidant effects", Nutr Res, 31, pp.387~396 (2011)[DOI]
  25. Shi SR, "Antigen retrieval technique utilizing citrate buffer or urea solution for immunohistochemical demonstration of androgen receptor in formalin-fixed paraffin sections", J Histochem Cytochem, 41, pp.1599~1604 (1993)[DOI]
  26. Barrett KL, "Advances in cytochemical methods for detection of apoptosis", J Histochem Cytochem, 49, pp.821~832 (2001)[DOI]
  27. Smyth PG, "Markers of apoptosis: methods for elucidating the mechanism of apoptotic cell death from the nervous system", Biotechniques, 32, pp.648~665 (2002)[DOI]
  28. Whittle BJ, "Attenuation of inflammation and cytokine production in rat colitis by a novel selective inhibitor of leukotriene A4 hydrolase", Br J Pharmacol, 153, pp.983~991 (2008)
  29. Lu P, "Enhanced experimental corneal neovascularization along with aberrant angiogenic factor expression in the absence of IL-1 receptor antagonist", Invest Ophthalmol Vis Sci, 50, pp.4761~4768 (2009)[DOI]
  30. Chell S, "Mediators of PGE2 synthesis and signaling downstream of COX-2 represent potential targets for the prevention", treatment of colorectal cancer, 2006, pp.1766, 104~119
  31. 유경미, "In vitro 상에서 유자(Citrus junos SIEB ex TANAKA) 용매 추출물의 암세포 억제효과 및 항산화성", 한국식품과학회지, 36(2), pp.339~344 (2004), 한국식품과학회
  32. Levene A, "Pathological factors influencing excision of tumours in the head and neck. Part I", Clin Otolaryngol Allied Sci, 6, pp.145~151 (1981)[DOI]
  33. Ludbrook J, "Update: microcomputer statistics packages. A personal view", Clin Exp Pharmacol Physiol, 24, pp.294~296 (1997)[DOI]
  34. Wilhelm SM, "BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF", MEK, Cancer Res, pp.2004, 64(19)[DOI]
  35. Eichbaum C, "Breast cancer cell-derived cytokines, macrophages and cell adhesion: implications for metastasis", Anticancer Res, 31(10), pp.3219~3227 (2011)
  36. Chell S, "Mediators of PGE2 synthesis and signalling downstream of COX-2 represent potential targets for the prevention", treatment of colorectal cancer, 2006, pp.1766(1), 104~119
  37. Chimenti MS, "Metabolic profiling of Human CD4+ cells follo wing treatment with methotrexate and anti-TNF-<TEX>${\alpha}$<", TEX> anfliximab, 2013, pp.12(18), 3025~3036
  38. Barton BE, "IL-6-like cytokines and cancer cachexia: consequences of chronic inflammation", Immunol Res, 23(1), pp.41~58 (2001)[DOI]
  39. Southan GJ, "Selective pharmacological inhibition of distinct nitric oxide synthase isoforms", Biochem Pharmacol, 51(4), pp.383~394 (1996)[DOI]
  40. Kostourou V, "The role of tumour-derived iNOS in tumour progression and angiogenesis", Br J Cancer, 104(1), pp.83~90 (2011)[DOI]
  41. Pan H, "Purification and identification of a polysaccharide from medicinal mushroom Amauroderma rude with immunomodulatory activity and inhibitory effect on tumor growth", Oncotarget, 6(19), pp.17777~17791 (2015)

관련 논문AI추천

이 간행물의 다른 논문 (12건)